Formation of bifunctional cross-linked products due to reaction of NAMI-A with DNA bases – a DFT study

Structural Chemistry - It is reported that NAMI-A and other Ru-anticancer complexes preferably bind with the N7 site of guanine and can also form DNA inter-strand cross-links. Therefore, in order...     

Meticulous assessment of natural compounds from NPASS database for identifying analogue of GRL0617, the only known inhibitor for SARS-CoV2 papain-like protease (PLpro) using rigorous computational workflow

Molecular Diversity - The latest global outbreak of 2019 respiratory coronavirus disease (COVID-19) is triggered by the inception of novel coronavirus SARS-CoV2. If recent events are of any...     

Combinational Chemotherapy and Photothermal Therapy Using a Gold Nanorod Platform for Cancer Treatment

Multimodal approaches combined with various nanomaterials and advanced techniques have been developed for synergistic cancer treatment. Among various therapies, conventional chemotherapy (CHT) is a direct cancer treatment that can produce unintended side effects due to nonspecific action on both the tumor and normal cells; patient-friendly photothermal therapy (PTT) may be able to treat embedded tumors in vital regions with minimal invasion but does not guarantee complete removal of cancers. However, the combination of CHT-PTT may provide a promising tool for direct cancer treatment with minimal side effects. In this regard, nanostructured materials, such as gold nanorods with tuned size and surface characteristics, are key components designed to enhance the heating capacity and active or passive delivery of drugs to the tumor site. In this review, the pioneering work synergizing CHT and PTT is summarized, and the current state-of-the-art in the development of inorganic and organic nanocomposites for combinational therapy is described.     

Ionic Assembly,Anion–π, Magnetic,and Electronic Attributes of Ambient Stable Naphthalenediimide Radical Ions

Organic spin-based molecular materials are considered to be attractive for the generation of functional materials with emergent optoelectronic, magnetic, or magneto-conductive properties. However, the major limitations to the utilization of organic spin-based systems are their high reactivity, instability, and propensity for dimerization. Herein, we report the synthesis, characterization, and magnetic and electronic studies of three ambient stable radical ions ( 1 a^.+ , 1 b^.+ , and 1 c^.+ ). The radical ions 1 b^.+ and 1 c^.+ with BPh₄⁻ and BF₄⁻ counter anions, respectively, were synthesized in excellent yields by means of anion metathesis of 1 a^.+ with Br⁻ as its counter anion. Notably, synthesis of 1 a^.+ was achieved in an ecofriendly, solvent-free protocol. The radical ions were characterized by means of single-crystal X-ray diffraction studies, which revealed the discrete nature of the radical ions and extensive hydrogen-bonding interactions within the radical ions and with the counter anions. Thus, radical ions can be organized to form infinite supramolecular arrays using weak noncovalent interactions. In addition, the Br⁻, BF₄⁻, and BPh₄⁻ anions formed diverse types of anion–π interactions with the naphthalene and imide rings of the radical ions. The radical ions were characterized by means of X-band electron paramagnetic resonance (EPR) spectroscopy in solution and in the solid state. Magnetic studies revealed their paramagnetic nature in the range of 10 to 300 K. The radical ions exhibited high resistivity approaching the gigaohm (GΩ) scale. In addition, the radical ions exhibited panchromism.     

Effect of polymer and ion concentration on mechanical and drug release behavior of gellan hydrogels using factorial design

Developing optimized hydrogel products requires an in-depth understanding of the mechanisms that drive hydrogel tunability. Here, we performed a full 4 × 4 factorial design study investigating the impact of gellan, a naturally derived polysaccharide (1%, 2%, 3%, or 4% w/v) and CaCl₂ concentration (1, 3, 7, or 10 mM) on the viscoelastic, swelling, and drug release behavior of gellan hydrogels containing a model drug, vancomycin. These concentrations were chosen to specifically provide insight into gellan hydrogel behavior for formulations utilizing polymer and salt concentrations expanding beyond those commonly reported by previous studies exploring gellan. With increasing gellan and CaCl₂ concentration, the hydrogel storage moduli (0.1–100 kPa) followed a power-law relationship and on average these hydrogels had higher liquid absorption capability and greater total drug release over 6 days. We suggest that the effects of gellan and CaCl₂ concentration and their interactions on hydrogel properties can be explained by various phenomena that lead to increased swelling and increased resistance to network expansion.     

Synergistic Biophysical Techniques Reveal Structural Mechanisms of Engineered Cationic Antimicrobial Peptides in Lipid Model Membranes

In the quest for new antibiotics, two novel engineered cationic antimicrobial peptides (eCAPs) have been rationally designed. WLBU2 and D8 (all 8 valines are the d -enantiomer) efficiently kill both Gram-negative and -positive bacteria, but WLBU2 is toxic and D8 nontoxic to eukaryotic cells. We explore protein secondary structure, location of peptides in six lipid model membranes, changes in membrane structure and pore evidence. We suggest that protein secondary structure is not a critical determinant of bactericidal activity, but that membrane thinning and dual location of WLBU2 and D8 in the membrane headgroup and hydrocarbon region may be important. While neither peptide thins the Gram-negative lipopolysaccharide outer membrane model, both locate deep into its hydrocarbon region where they are primed for self-promoted uptake into the periplasm. The partially α-helical secondary structure of WLBU2 in a red blood cell (RBC) membrane model containing 50 % cholesterol, could play a role in destabilizing this RBC membrane model causing pore formation that is not observed with the D8 random coil, which correlates with RBC hemolysis caused by WLBU2 but not by D8.     

Carbon nanotube dielectrophoresis: Theory and applications

Carbon nanotubes (CNTs) are one of the most extensively studied nanomaterials in the 21st century. Since their discovery in 1991, many studies have been reported advancing our knowledge in terms of their structure, properties, synthesis, and applications. CNTs exhibit unique electrothermal and conductive properties which, combined with their mechanical strength, have led to tremendous attention of CNTs as a nanoscale material in the past two decades. To introduce the various types of CNTs, we first provide basic information on their structure followed by some intriguing properties and a brief overview of synthesis methods. Although impressive advances have been demonstrated with CNTs, critical applications require purification, positioning, and separation to yield desired properties and functional elements. Here, we review a versatile technique to manipulate CNTs based on their dielectric properties, namely dielectrophoresis (DEP). A detailed discussion on the DEP aspects of CNTs including the theory and various technical microfluidic realizations is provided. Various advancements in DEP-based manipulations of single-walled and multiwalled CNTs are also discussed with special emphasis on applications involving separation, purification, sensing, and nanofabrication.     

Weakly Nonlinear Waves in Nonideal Fluids

We study the propagation of weakly nonlinear waves in nonideal fluids, which exhibit mixed nonlinearity. A method of multiple scales is used to obtain a transport equation from the Navier–Stokes equations, supplemented by the equation of state for a van der Waals fluid. Effects of van der Waals parameters on the wave evolution, governed by the transport equation, are investigated.     

Synthetic Heparanase Inhibitors Can Prevent Herpes Simplex Viral Spread

Herpes simplex virus (HSV-1) employs heparan sulfate (HS) as receptor for cell attachment and entry. During late-stage infection, the virus induces the upregulation of human heparanase (Hpse) to remove cell surface HS allowing viral spread. We hypothesized that inhibition of Hpse will prevent viral release thereby representing a new therapeutic strategy for HSV-1. A range of HS-oligosaccharides was prepared to examine the importance of chain length and 2-O-sulfation of iduronic moieties for Hpse inhibition. It was found that hexa- and octasaccharides potently inhibited the enzyme and that 2-O-sulfation of iduronic acid is tolerated. Computational studies provided a rationale for the observed structure–activity relationship. Treatment of human corneal epithelial cells (HCEs) infected with HSV-1 with the hexa- and octasaccharide blocked viral induced shedding of HS which significantly reduced spread of virions. The compounds also inhibited migration and proliferation of immortalized HCEs thereby providing additional therapeutic properties.     

Synthesis and Biological Studies of O3-Aryl Galactosides as Galectin Inhibitors

β-Galactose derivatives have recently been reported to selectively inhibit galectin-3, and a library of O3-arylated galactosides with varying substitution patterns was designed to study such inhibitions further. The O3-arylated galactosides were synthesized using diaryliodonium salts under mild and transition metal free conditions, providing the target products in moderate to good yields. An O3-trifluoroethylated galactoside was also synthesized using iodonium salt chemistry. Azido-substituted products were subsequently transformed into the corresponding triazoles. After deprotection, a selection of galactoside derivatives were evaluated for inhibitory potencies against galectins-1, 3, 4 N (N-terminal domain), 4 C (C-terminal domain), 7, 8 N, 8 C, 9 N, and 9 C and one compound with promising affinity and selectivity for both the N- and C-terminal domain of galectin-9 was discovered.